Paneth cells are a common cell type in human small intestine, located at the base of most, if not all, crypts. Despite their prevalence, very little is known about their function. Recent observations from our laboratories indicate that they can phagocytose and kill microorganisms and that IgA and IgG are present in amounts greater than in surrounding crypt epithelial cells. Lysozyme, an enzyme capable of degrading a peptidoglycan component of bacterial cell wall, is also present. These findings have led to the hypothesis that Paneth cells function to regulate microbial flora within the intestinal crypts. The objectives of this proposal are 1) to investigate the role of the Paneth cell in the defense system of the rat and human small intestine and 2) to study this cell in selected gastrointestinal diseases. Specific research aims include 1. characterization of the effects of manipulation of bacterial flora and Paneth cell secretion on Paneth cell numbers and IgA content, 2. ultrastructural localization of IgA within Paneth cells, 3. studies of the phagocytic capability of Paneth cells, and 4. evaluation of Paneth cell morphology in several gastrointestinal diseases. Methods for most of these projects will be based on immunohistochemical techniques for localization of antigen in tissues.